The oleander aphid, Aphis nerii Boyer de Fonscolombe, feeds on members of the Apocynaceae family, including several Asclepias species and Cynanchum laeve. Milkweeds alongside and within agricultural crops provide opportunities for natural enemies to encounter and feed upon A. nerii. The predator fauna associated with natural populations of A. nerii on four milkweed species was determined. The development and fecundity of two Coccinellidae species, Harmonia axyridis (Pallas) and Cycloneda munda (Say), were investigated in a laboratory. The development of fourth instar Coccinellidae when fed diets containing A. nerii from host plants having a low or high concentration of cardenolides was investigated. Immature beetle survival was generally poor and longevity was not significantly different when fed A. nerii from different host plant species, with similar survival patterns observed for first and fourth instar Coccinellidae larvae. Both H. axyridis and C. munda exhibited a reduced fecundity when fed A. nerii regardless of milkweed host species compared to beetle fecundity when fed a diet of Acyrthosiphon pisum. When provided with mixed diets, larvae consumed significantly more A. pisum than A. nerii. Larvae continued to accept A. nerii even after feeding on the aphid provoked emesis. Observations revealed that a fluid leaked from within wounded aphids temporarily or permanently immobilized lady beetle larvae. The unsuitability of A. nerii for lady beetles and the common association of milkweeds with agroecosystems raises concerns about the possible effects of feeding on this aphid by biological control agents.